ES2704665T3 - Extract of pulp and / or avocado skin rich in polyphenols and cosmetic, dermatological and nutraceutical compositions that comprise it - Google Patents

Abstract

Avocado fruit extract rich in polyphenols, which contains at least 10% by weight of polyphenols and advantageously between 10 and 30% by weight of polyphenols, expressed in equivalent of gallic acid with respect to the dry extract obtained, containing said polyphenols a mixture of procyanidins, caffeic acid and derivatives of caffeic acid, in a proportion of at least 70% by weight, expressed in equivalent of gallic acid with respect to the total weight content of polyphenols, and which also comprises at least 10%, advantageously 10 to 60% of avocado sugars, said sugars containing at least Dmanoheptulose and / or perseitol, the percentages being expressed by weight with respect to the weight of the dry extract, characterized in that it is obtainable by extraction of Avocado fruits that dried in a first phase, in mild conditions, and then slipped, and because it is likely to be obtained by solid-liquid extraction A part of the avocado fruit is used in a solvent consisting of a binary mixture of water-type solvents and a solvent selected from glycerol or a glycol such as propanediol.

Description

DESCRIPTION

Extract of pulp and / or avocado skin rich in polyphenols and cosmetic, dermatological and nutraceutical compositions that comprise it.

The invention relates to an extract of avocado fruit, in particular of pulp and / or avocado skin, rich in polyphenols, and to cosmetic, pharmaceutical, dermatological, nutraceutical compositions comprising such extract and, optionally, an appropriate excipient .

Another subject of the invention is a process for extracting an avocado extract rich in polyphenols, as well as the extract obtainable by said process.

The invention also relates to such a composition or such an extract for use in the prevention or treatment of disorders or pathologies of the skin, mucous membranes or skin. The invention finally relates to a method of cosmetic care of the skin, of the skin or of the mucous membranes, in order to improve its condition or appearance, which consists in administering such composition or such extract.

The avocado (Persea americada or Persea gratissima) belongs to the family of leuraceae.

There is a great diversity of avocado varieties. Among the most widespread, we can mention the varieties Hass, Fuerte, Ettinger, Bacon, Nabal, Ananheim, Lula, Reed, Zutano, Quenn, Criola Selva, Mexicana Canta, Tegion Dschang, Hall, Booth, Peterson, Collinson Redn. Notably, the varieties Hass, Fuerte, Ettinger and Bacon, and more advantageously the Hass and Fuerte varieties. The weight of the fruits can vary from 50 g to more than 1 kg. It is constituted by 10 to 20% for the bone, 7 to 15% for the teguments, and 65 to 80% for the pulp. The skin is of variable thickness, texture and color, from smooth to rough, generally green but that can turn brown, violet to black.

The pulp is of variable flavor and color and is constituted, on average, by:

Table 1: composition of the avocado pulp; * Wei Wang, Food Chemistry, 122: 1193-1198 (2010).

The avocado pulp is widely used by South American populations to shine the hair. Some topical applications of pulp on the skin are also very frequent for their antioxidant and nutrient activity, related to the nature of the lipids that compose it (fatty acids and unsaponifiable fraction - vitamin E).

Fruits, particularly their pulp, are commonly used in folk medicine in the tropics. They are very rich in vitamins A, B, C, D, E and K and recommended for diabetics. The pulp would also be ascaricide (and vermifuge), aphrodisiac and tonic. It is used in South America in poultices to improve the boils and the whitlow. It has been shown that a high intake of avocados had an effect on blood cholesterol levels. In particular, after 7 days of a diet rich in avocados, some patients with hypercholesterolemia have seen their percentage of total cholesterol decrease by 17%. These subjects have also shown a 22% decrease in LDL (bad) cholesterol and triglyceride levels, and an 11% increase in (good) HDL cholesterol. Its monounsaturated fatty acids are excellent for cardiovascular health and good blood cholesterol (HDL). In addition, the avocado is a very good source of fibers (soluble and insoluble) and antioxidants.

A very broad family of molecules, very widespread in the plant world, characterized by the presence of one or several phenolic nuclei, which include in particular the following subfamilies, is designated under the name "polyphenols":

• phenolic acids (cinnamic and benzoic);

• flavonoids, quasi-universal pigments of vegetables, responsible for the coloring of flowers, fruits and sometimes leaves. It is in this family the anticianos (color blue, to violet happening through the red one);

• quinones and anthraquinones and some derivative condensed forms; Y

• more complex and polymerized forms: the hydrolysable tannins derived from gallic and ellagic acid; condensed tannins derived from catéquic acid, OPC or proanthocyanidols.

These molecules are known for their numerous biological activities (anti-oxidants, anti-inflammatory, anti-bacterial) and are used both in the fields of pharmacy, cosmetics and nutrition / food supplements depending on some specific structures.

Polyphenols are widely distributed in many families of the higher plant kingdom as they are frequently indispensable for their survival: protection against different external aggressions (UV, dryness, microorganisms, ...).

Among the most widespread and exploited polyphenols, we can mention: polyphenols tea (Camomellia sinensis), grape (Vitis vinifera), cocoa (Cocoa theobroma). Application FR 2928263 describes compositions comprising an association of plant polyphenols (apple polyphenols are particularly described) and vegetable sugars. The polyphenols sought are polymeric polyphenols, and in particular procyanidins and prodelfinidins. Avocado is not cited as a source of sugars.

The international application WO 2005/105123 discloses a medicament comprising a peptide extract of avocado and which may also comprise a composition containing D-mannoheptulose and / or perseitol.

The international application WO 2005/115421 describes the use of a compound comprising D-manheptulose and / or perseitol to produce a medicament for treating and / or preventing diseases related to the modification of an innate and / or acquired immunity by increasing the production of antimicrobial peptides, preferably hBD-2 without inducing inflammatory reactions, irritation or intolerance. Said compound may also comprise a peptide extract of avocado and / or a peptide extract of lupine. The inventors have discovered that the extracts of avocado (Persea gratissima or americana) rich in polyphenols have cosmetic, dermatological, pharmaceutical or nutraceutical properties, in particular cosmetic and dermatological properties, never described before. In particular, it is the first time that extracts rich in avocado polyphenols are used as such, due to their specific properties.

The invention has as its object, in particular:

- an extract of avocado fruit rich in polyphenols, containing at least 10% by weight of polyphenols, expressed in gallic acid equivalent with respect to the dry extract obtained, said polyphenols being procyanidins, caffeic acid and some derivatives of the caffeic acid in a proportion of at least 70% by weight expressed in gallic acid equivalent to the total weight content of polyphenols. In particular, the extract contains from 10 to 30% by weight of polyphenols, expressed in gallic acid equivalent with respect to the weight of the dry extract. The proportions in procyanidins, caffeic acid and caffeic acid derivatives in said polyphenols are advantageously at least 80%, by weight expressed in gallic acid equivalent to the total weight content of polyphenols.

The procyanidins are advantageously selected from the group consisting of the dimeric procyanidins of type B, the trimeric procyanidins of type A and B and the tetrameric procyanidins of type A and B.

In the polyphenols contained in this extract, there is advantageously at least 30% by weight of procyanidins, expressed in gallic acid equivalent with respect to the total weight content of polyphenols. In the polyphenols contained in this extract, caffeic acid and its derivatives are advantageously found, typically in a proportion of at least 30% by weight, expressed in gallic acid equivalent to the total weight content of polyphenols.

The extract also comprises at least 10%, advantageously from 10 to 60% of avocado sugars, said sugars containing at least D-manheptulose and / or perseitol; the percentages by weight are expressed with respect to the total weight of the dry extract.

The extract is capable of being obtained by extracting avocado fruits that were dried in a first phase, under mild conditions, and then delipidated.

The extract is capable of being obtained by solid-liquid extraction of a part of the fruit of the avocado in a solvent consisting of a binary mixture of water-type solvents and a solvent selected from glycerol or a glycol such as propanediol, advantageously in proportions comprised between 0% and 100% of water with respect to other solvents.

- a composition comprising as active an extract according to the invention and, advantageously, an appropriate excipient. In particular, the composition is a cosmetic, pharmaceutical, dermatological or nutraceutical composition.

The composition also advantageously comprises another active ingredient, in particular selected from the group consisting of the emollients, the moisturizing active agents, the keratimulators, the keratolytics, the healing and / or restructuring agents of the skin barrier, the PPAR, RXR or LXR agonists, seborregulatory agents, anti-irritant and / or anti-inflammatory agents and / or painkillers, anti-oxidants, anti-aging agents, depigmenting or hypopigmentation agents, pigmenting agents, lipolytic agents or lipogenesis inhibitors or also anti-cellulite agents or slimming, mineral or organic filters and sunscreens (pigmentary or ultrafine), antifungal compounds, preservatives, antibacterial agents, prebiotics and probiotics, antibiotics and immunomodulators.

The composition advantageously comprises another active agent, an agent useful in the treatment of acne, in particular selected from the group consisting of the inhibitors of 5-alpha reductase, zinc (and its salts gluconate, salicylate and pyroglutamic acid), spironolactone , linoleic acid, antibiotics, benzoyl peroxide, azelaic acid, vitamin PP, vitamin B3, cyclins, giant pumpkin seed extracts, pumpkin seed oil and sabal.

- an extract or a composition according to the invention for its use as a pharmaceutical, dermatological or cosmetic composition or as a functional food; in particular for use in the prevention and / or treatment of disorders or pathologies of the skin and / or mucous membranes and / or of the facets, more particularly for their use in the prevention and / or treatment of reactions or allergic, inflammatory, irritative pathologies or disorders of the barrier or homeostasis of the skin, or vascular disorders, or as depigmenting or healing agent.

- a procedure for cosmetic care of the skin and / or of the facets and / or mucous membranes, in order to improve their condition and / or appearance, which consists of administering a composition or an extract according to the invention. Avocado extract rich in polyphenols is an extract obtained by means of processes that allow the polyphenols potentially present in the avocado to be concentrated, so that this extract contains at least 10% by weight of polyphenols, expressed in gallic acid equivalent. regarding the weight of the dry extract. According to an advantageous variant of the invention, the extract contains from 10% to 30% by weight of polyphenols, more advantageously from 10% to 20% by weight of polyphenols, expressed in gallic acid equivalent to the dry extract obtained.

The content of the dry extract in the extract according to the invention, expressed by weight with respect to the total weight of the extract, varies from 0.01 to 90%, advantageously from 0.5 to 50%, more advantageously from 0.5 to 15% , even more advantageously from 0.5 to 5%.

In the polyphenols contained in this extract, there are procyanidins, caffeic acid and caffeic acid derivatives, in particular esterified derivatives, in a proportion of at least 70%, advantageously of at least 80%, more advantageously of at least 90%, still more advantageously of at least 95% by weight, expressed in gallic acid equivalent with respect to the total weight content of polyphenols.

The procyanidins are oligomers of catechins / epicatechin. The catechin and the epicatechin are respectively the optical isomers (+) and (-) of the molecule corresponding to the following formula (I):

The procyanidins are advantageously dimeric procyanidins of type B. The procyanidins of type B-1, B-2, B-3 and B-4 are dimers formed from two (+) - catechin and (-) - epicatechin units , joined in C ⁴ -Ca. The procyanidins of type B-5, B-6, B-7 and B-8 are dimers formed from two (+) - catechin and (-) - epicatechin units, joined in C ⁴ -C ⁶ .

The procyanidins are also advantageously trimeric procyanidins of type A and B.

The procyanidins are also advantageously tetrameric procyanidins of type A and B.

The procyanidins are also advantageously oligomeric or polymeric procyanidins (number of catechin or epicatechin units> 4).

In the polyphenols contained in this extract, advantageously at least 30%, more advantageously at least 50% by weight of procyanidins, expressed in gallic acid equivalent with respect to the total weight content of polyphenols.

In the polyphenols contained in this extract, caffeic acid and its derivatives are also advantageously present in a proportion of at least 20%, more advantageously at least 30% by weight, expressed in gallic acid equivalent with respect to the content in total weight of polyphenols.

The caffeic acid responds to the following formula (II):

Caffeic acid and its derivative, the phenethyl coffee ester (ester of caffeic acid and 2-phenylethanol), are present in numerous plants, and in particular in large quantities in coffee, from which it derives its name. The caffeic acid may be present in esterified form, for example with the quinic acid with which it forms the chlorogenic acid. Among the other esterified forms, mention may be made of caffeoaryrtaric acid (or kaftalic acid) formed with tartaric acid, caffeoylsichimic acid (formed with the chemical acid), caffeoylmalic acid (formed with malic acid), or also esterified with glucose (caffeoylglucose) or in the form of amide with putrescine (caffeoilputrescine).

Other phenols may also be present in the extract according to the invention, but are nonetheless minor. Its content by weight, expressed in gallic acid equivalent to the total weight content of polyphenols, is advantageously less than 30%, more advantageously less than 20%, even more advantageously less than 10%, even more advantageously less than 5% , even more advantageously less than 2%.

The extract contains at least 10%, advantageously from 10 to 60%, more advantageously from 10 to 30%, of avocado sugars, typically said sugars contain at least D-mannoheptulose and / or perseitol (% are expressed in weight with respect to the weight of the dry extract).

Within the scope of the present invention, the terms "D-mannoheptulose" and "perseitol" also cover their chemical derivatives.

The sugars in the avocado are essentially D-mannoheptulose, perseitol, sucrose, glucose and fructose. Traces of other sugars can be found, but their content is less than 5% by weight, advantageously less than 2% by weight, with respect to the total weight of the avocado sugars.

In the extract according to the invention, the total proportion in D-mannoheptulose and / or in perseitol in the sugars of avocados is advantageously at least 50% by weight, based on the total weight content of the sugars. More advantageously, the total proportion in D-mannoheptulose and / or in perseitol in the avocado sugars is 50% to 98% by weight, more advantageously 55% to 95% by weight, even more advantageously 60% to 90% in weight, with respect to the total weight content of sugars.

The mass ratio D-manheptulose: perseitol advantageously ranges from 1:10 to 10: 1.

The extract according to the invention advantageously contains from 0 to 50% by weight, more advantageously from 0 to 20% by weight, even more advantageously from 0 to 10% by weight, of lipids of avocados; the% by weight being expressed with respect to the total weight of the dry extract.

The extract according to the invention advantageously contains from 0 to 60% by weight, more advantageously from 1 to 30% by weight, even more advantageously from 5 to 15% by weight, of avocado proteins; the weight% is expressed with respect to the total weight of the dry extract (Bradford evaluation).

The extract according to the invention is obtained by extracting a part of the avocado fruit, preferably from the pulp and / or the skin. The residual cake from the pressing of the dried avocado pulp is more particularly used. Said pulp has been previously dried under mild conditions before the extraction of the lipids. It is particularly advantageous to use fruits (pulp and / or skin) of avocados that have dried in a first time, in mild conditions, and then delipidated. In fact, it has been found that under such conditions, optimal preservation of the polyphenols is ensured by inactivation of the polyphenoloxidase when drying takes place (it is even possible to obtain extracts that do not contain polyphenoloxidase).

Advantageously, this extract is obtained by solid-liquid extraction of a part of the fruit of the avocado in a solvent consisting of a binary mixture of water-type solvents and a solvent selected from glycerol or a glycol such as propanediol. The parts of the fruit preferably retained are the dried and / or deoiled pulp (cake) and / or the skin, more preferably the pulp dried under mild conditions and then de-oiled.

The solvent is advantageously in proportions comprised between 0% and 100% water with respect to other solvents.

Mostly, binary mixtures of water-type solvents and a solvent selected from glycerol or propanediol are used.

More particularly, between 0.1 and 50% by weight (expressed with respect to the total weight of avocado solvent) of dry part of avocado in the extraction solvent, and preferably 10% by weight, will be introduced. In the presence of glycerol, a concentration between 40% and 90% of glycerol, and preferably between 60% and 80% (the% are by weight of glycerol with respect to the total weight of glycerol water) will be preferably chosen.

In the presence of glycol, and more particularly of propanediol, a proportion between 40% and 80%, and advantageously between 50% and 60% of propanediol with respect to water (% are by weight of propanediol, are preferably chosen. with respect to the total weight of water, propane diol).

The extraction temperature is advantageously between 4 ° C and 100 ° C, and preferably between 10 ° C and 60 ° C, and more particularly between 15 ° C and 30 ° C.

The duration of extraction advantageously ranges from 30 minutes to 4 hours, more particularly from 30 minutes to 2 hours.

These different extractions can be followed by purification stages by ultrafiltration (cut-off threshold of 10 kDa for example), or diafiltration and / or nanofiltration (cut-off threshold of 200 Da for example), which allows to concentrate the polyphenols at the expense of the sugars (of which the specific sugars of C7 avocado, manoheptulose and perseitol).

The extract obtained after these purification steps advantageously comprises 10% to 30% by weight of polyphenols, even more advantageously from 10% to 20% by weight of polyphenols, expressed in gallic acid equivalent to the weight of the dry extract.

The content of sugars in the extract obtained after these purification steps is advantageously between 5 and 20% by weight, based on the weight of the dry extract.

The sugars present in this extract advantageously comprise from 20 to 60% of D-mannoheptulose and / or of perseitol, more advantageously from 30 to 60% of D-man- faheptulose and / or of perseitol, expressed by weight with respect to the total weight of sugars .

The extract obtained may be presented in liquid form, but may also be dried according to the procedures known to the person skilled in the art, atomization or lyophilization, for example, with or without support such as maltodextrin.

The subject of the invention is also a process for preparing an avocado extract rich in polyphenols comprising the following successive stages:

(a) dispersing in liquid phase in a suitable solvent the fruit (advantageously pulp and / or skin) of the avocado, and advantageously of the dried deoiled pulp (cake);

(b) subjecting the mixture obtained after step (a) to an extraction under stirring in an aqueous and / or alcoholic and / or glycolic and / or glycerol solvent, advantageously a mixture of water and a solvent selected from the group constituted by ethanol, glycerol, glycol (advantageously propanediol) and their mixtures; in a proportion advantageously of 60% of these solvents in water;

(c) centrifuging the extract obtained after step (b) and then filtering or filtering directly;

(d) where appropriate, subjecting the extract obtained after step (c) to an ultrafiltration and / or diafiltration and / or nanofiltration stage;

(e) after step (c) or (d), recover the extract rich in polyphenols; Y

(f) optionally drying the extract obtained after step (e) on a support or not.

The extract is advantageously used as an active agent in a cosmetic, pharmaceutical, dermatological or nutraceutical composition, which may comprise one or more suitable excipients. The composition may further comprise at least one other active compound in addition to the avocado extract rich in polyphenols. This other compound can be selected from among all the compounds and their functional equivalents, listed above.

This other compound can be selected in particular from active ingredients conventionally used in dermatology, pharmaceuticals, cosmetics or nutraceuticals, and known to the person skilled in the art such as emollients, moisturizing active agents, kerateregulators, keratolytics, scarring and / or restructuring agents of the skin barrier, PPAR, RXR or LXR agonists, seborregulatory agents, anti-irritant and / or anti-inflammatory agents and / or painkillers, antioxidants, anti-aging agents, depigmenting or hypopigmentation agents, pigmenting agents, lipolytic agents or inhibitors of lipogenesis or also anti-cellulite or slimming agents, mineral or organic (pigmentary or ultrafine) sunscreens and filters, antifungal compounds, preservatives, antibacterial agents, pre and probiotic agents, antibiotics, immunomodulators.

More particularly, the curative and / or restructuring agents of the cutaneous barrier that can be used in combination are advantageously panthenol (vitamin B5), arabinogalactan, zinc oxide, ceramides, cholesterol, squalane and phospholipids.

Seboregulatory agents that can be used in combination are advantageously selected from the group consisting of the 5-alpha reductase inhibitors, such as zinc and its derivatives (gluconate, silicilate and pyroglutamic acid salts).

The anti-inflammatory and / or anti-irritant and / or calming agent can be arabinogalactan.

Among the hypopigmenting or depigmenting agents, mention may be made of N-undecylenyl-L-phenylalanine (Sepiwhite®).

The sunscreen agents that can be used in combination are advantageously UVB and / or UVA filters or sunscreens; such as the screens or the mineral and / or organic filters known to the person skilled in the art, which will adapt their choice and their concentrations depending on the degree of protection sought.

The preservatives that can be used in combination are, for example, those generally used in cosmetics or in nutraceuticals, the molecules with antibacterial activity (pseudo-preservatives) such as caprylic derivatives such as, for example, capryloylglycine and glycerylcaprylate; hexanodiol, sodium levulinate, and zinc and copper derivatives (gluconate and PCA).

Among the active ingredients recommended in association with the extract according to the invention, mention may be made of plant extracts, in particular:

- vegetable oils such as soybean oils and / or rapeseed oil, avocado oil (WO2004 / 012496, WO2004 / 012752, WO2004 / 016106, WO2007 / 057439), lupine oil, advantageously lupine oil sweet white (WO 98/47479), or a mixture of these oils;

- oil diatomaceous or concentrates of vegetable or animal oil, especially sunflower, more advantageously linoleic sunflower concentrates, such as sunflower oil concentrated in unsaponifiables (Soline®) (see international application WO 01/21150) marketed by the Laboratorios Expanscience, the oils concentrated in unsaponifiables of avocado oil, rapeseed, corn or palm oil, useful in particular for their moisturizing and / or emollient activity, healing and / or restructuring of the skin barrier, anti-inflammatory and / or anti-irritant and / or calming;

- the unsaponifiables of vegetables or vegetable oil, advantageously avocado furans (Avocadofurane®), which can be obtained by the process described in the international application WO 01/21605, the unsaponifiables of avocado and / or soy, more particularly a mixture of unsaponifiables of furan avocado and soy unsaponifiables, advantageously in a respective ratio of approximately 1 / 3-2 / 3 (such as Piasclédine®), soybean unsaponifiables (as obtained according to the process described in the international application WO01 / 51596), the unsaponifiables sterol (typically unsaponifiables whose content in sterols, in methyl sterols and in triterpene alcohols is comprised between 20 and 95% by weight, preferably 45-65% by weight, with respect to the total weight of unsaponifiable) , phytosterols, sterol esters and vitamin derivatives, useful in particular for their healing and / or restructuring activity of the skin barrier, anti-aging, anti-inflammatory;

- peptides or complexes of plant amino acids, in particular avocado peptides (such as those described in international application WO2005 / 105123), lupine peptides (such as those obtained according to the process described in application WO2005 / 102259), the quinoa peptides (such as those described in the international application WO2008 / 080974), the Maca peptides such as those described in international application WO2004 / 112742), the soybean peptides fermented or not, the rice peptides (such as those described in the international application WO 2008/009709), useful in particular for its moisturizing and / or emollient (avocado), keratoregulatory (lupine, quinoa), healing and / or restructuring of the cutaneous barrier (maca, quinoa, soy) activity , anti-inflammatory and / or anti-irritant and / or calming (lupine, quinoa), antioxidant (avocado), anti-aging (lupine, maca), pigmenting (rice);

- vegetable sugars, in particular avocado sugars (such as those described in the application WO2005 / 115421), especially useful for their querateregulatory, healing and / or restructuring properties of the skin barrier, anti-inflammatory and / or anti-irritant and / or painkillers;

- butyl avocatete (5 alpha Avocuta®), inhibitor of 5-alpha reductase (see WO 01/52837 and WO 02/06205), typically regulating seborrhea secretion that is increased in acne or dandruff ;

- extracts rich in polyphenols, and more particularly extracts of aerial parts of Ginandropsis gyandra (FR 1061051) and extracts of Maca leaf (FR 1061047);

- the lupeol (FR 2822821, FR 2857596) useful in particular to promote healing,

- a total extract of lupine (such as those described in international application WO2005 / 102259), particularly adapted for the treatment of irritations;

- an extract of Acacia macrostachya seeds (FR 0958525), an extract of maca leaves (FR 1061047), a seed extract of Schizandra sphenanthera (FR 0955343 and FR 0955344) and seeds of Vigna unguiculata (FR 0958529).

Among the active ingredients recommended in association with the extract according to the invention, mention may be made of oxazolines, in particular those selected from the group consisting of 2-undecyl-4-hydroxymethyl-4-methyl-1,3-oxazoline, undecyl-4,4-dimethyl-1,3-oxazoline, (E) -4,4-dimethyl-2-heptadec-8-enyl-1,3-oxazoline, 4-hydroxymethyl-4-methyl-2- heptadecyl-1,3-oxazoline, (E) -4-hydroxymethyl-4-methyl-2-heptadec-8-enyl-1,3-oxazoline, 2-undecyl-4-ethyl-4-hydroxymethyl-1, 3-oxazoline, preferably 2-undecyl-4,4-dimethyl-1,3-oxazoline (OX-100 or Cyclocéramide®, WO2004050052, WO2004050079, and WO2004112741). They are particularly useful for their anti-inflammatory and / or anti-irritant and / or calming, antioxidant, depigmenting, immunomodulating activities.

Among the active ingredients recommended in association with the extract according to the invention, mention may be made of 5-alpha reductase inhibitors, such as butyl avocatete (5 alpha Avocuta®).

All of these associations comprise at least one other active compound, in addition to the avocado extract rich in polyphenols, and may comprise two, three, four or more active compounds such as described above.

The composition according to the invention can be formulated in the form of different preparations adapted for topical administration, oral, rectal, vaginal, nasal, auricular or bronchial administration, as well as parenteral administration.

According to a first variant, the different preparations are adapted for topical administration and include especially creams, emulsions, milks, ointments, lotions, oils, aqueous or hydro-alcoholic or glycolic solutions, powders, patches , sprays, shampoos, enamels or any other product for external application.

According to a second variant, the different preparations are adapted for an oral administration; the Avocado extract rich in polyphenols can enter either a food supplement or a nutraceutical composition. The food supplement may be in the form of the avocado extract rich in polyphenols as such or in the form of hard capsules or soft gelatine or vegetable capsules within the scope of the present invention. Said food supplement can then contain from 10 to 100% by weight of the avocado extract rich in polyphenols.

The composition of the present invention can be incorporated directly and without further modification in nutraceuticals, especially hyperproteined dietary products or concoctions, thanks to techniques such as mixing, infusion, injection, mixing, absorption, kneading and mixing. spray.

The modes of administration, dosages and optimal galenic forms of compounds and compositions according to the invention can be determined according to the criteria generally taken into account in the establishment of a pharmaceutical treatment, in particular dermatological, cosmetic or veterinary treatment adapted to a patient or a animal, such as the age or body weight of the patient or animal, the severity of their general condition, tolerance to treatment, side effects noted, type of skin. Depending on the type of administration desired, the composition and / or the active compounds according to the invention may further comprise at least one pharmaceutically acceptable excipient, in particular dermatologically acceptable, or a cosmetically acceptable or nutraceutically acceptable excipient. According to the first variant, an excipient adapted for external topical administration is used. The composition according to the present invention may further comprise at least one pharmaceutical or cosmetic adjuvant known to the person skilled in the art, selected from among the thickeners, the preservatives, the perfumes, the dyes, some chemical or mineral filters, the moisturizing agents, the thermal waters, etc.

The composition comprising an avocado extract rich in polyphenols having the specified specifications is particularly intended for cosmetic, pharmaceutical or dermatological use. The composition will be advantageously formulated in the form of a preparation adapted for topical administration.

The subject of the invention is also the use of an avocado extract rich in polyphenols, for the manufacture of a cosmetic, pharmaceutical, dermatological composition, of a nutraceutical composition or of a functional food.

Advantageously, the composition or extract according to the present invention is used in the prevention and / or treatment of the disorders or pathologies of the skin and / or of the mucous membranes and / or of the ducts.

In particular, the composition or extract according to the invention is intended for the prevention and / or treatment of allergic, inflammatory, irritative reactions or pathologies or disorders of the barrier or skin homeostasis of the skin ( hair and nails) and / or mucous membranes (gums, periodontium, genital mucous membranes) immature (s), normal (s) or mature (s) / aged (s).

It is understood by disorders of the skin barrier, of the skin and / or mucous membranes, the disorders that take part at the level of the outer layer of the epidermis.

It is understood by disorders of the homeostasis of the skin, of the faneras and / or of the mucous membranes, the disorders that result from the processes of renewal and balance of the cells such as psoriasis, dermatitis of the seat, the atopic dermatitis, Dry skin (xerosis), dehydrated skin and photosensitized skin.

Advantageously, the composition or extract according to the invention can be used for the prevention and / or treatment of reactions, disorders or pathologies:

- of the skin, such as rosacea or erythrocuperosis, psoriasis, vascular disorders, seat dermatitis, atopic dermatitis, eczema, contact dermatitis, irritant dermatitis, allergic dermatitis, seborrheic dermatitis (milk crust) ), sensitive skin, reactive skin, itching, dry skin (xerosis), dehydrated skin, skin with redness, skin erythema, aged or photo-aged skin, photosensitized skin, pigmented skin (melasma, pigmentation) post-inflammatory), skin with cellulitis, sagging skin, skin with stretch marks, herpes, cracks, bites, cracks, in particular of sinuses, sunburn, inflammations due to the rays of any type, irritations by chemical agents, physical (for example skin tensions for pregnant women), bacteriological, fungal or viral, parasitic (lice, scabies, tinea, mites, dermatophytes), radiological or for deficiency of innate immunity (antimicrobial peptides) or acquired (cellular, humoral, cytokines), and / or

- of the mucous membranes, such as the gums and the periodontium, which can present some gingivitis (sensitive gums of newborns, hygiene problems, due to smoking or others), periodontal diseases, or genital mucous membranes that can present irritations of male genital spheres or external or internal females, and / or

- of the phantoms such as nails (brittle, brittle nails, etc.) and of hair (alopecia, dandruff, hirsutism, seborrheic dermatitis, folliculitis) immature, normal or mature, presenting in particular disorders of the scalp such as alopecia (or baldness) androgenetic, acute, localized, cicatricial, congenital, occipital of the infant, areata, due to chemotherapy / radiotherapy or also telogen effluvium, anagen effluvium, pillar dystrophy, trichotillomania, tinea or oily dandruff or dry.

The composition or extract according to the present invention is also advantageously used in the prevention and / or treatment of vascular disorders, and can be used advantageously in depigmentation by reduction of melanin and / or inhibition of tyrosinase, or as a healing agent .

The invention also relates to a method of cosmetic care of the skin and / or of the facets and / or of the mucous membranes, in order to improve their condition and / or appearance, which comprises the administration or which consists in administering a cosmetic composition or an extract according to the present invention.

In one embodiment of the cosmetic method according to the invention, the skin and / or the ducts and / or the mucous membranes considered are advantageously those which are sensitive, irritated, assaulted by the environment (UV, pollution), in particular the sensitive skins.

The cosmetic process according to the invention is also characterized in that the composition or extract is used as a moisturizing product, or as a chronological or photo-induced anti-aging product in the prevention of aging, and photo-induced aging, or as a slimming product and / or anti-cellulite, or also as anti-aging product or anti-stain product.

By "moisturizing product" is meant a product which makes it possible in particular to prevent and / or treat disorders of the barrier or of the homeostasis of the skin, of the skin and / or mucous membranes.

An anti-stain product is understood as a product that makes it possible to reduce pigmentation spots on the skin and / or on the facets and / or mucous membranes.

Slimming and / or anti-cellulite product is understood as a product that allows to improve the firmness, elasticity or tonicity of the skin, and / or to fight against the accumulation of adipose tissue and the skin with cellulitis.

Example 1 - comparative

The dried and de-oiled avocado pulp (cake) is suspended under stirring at 10% in a 60/40 w / w ethanol / water mixture for 1 h at room temperature. The residual dry matter is separated from the liquid phase either by filtration, decantation or centrifugation, and the liquid phase thus obtained can be filtered with the aid of filters of adapted porosity in order to obtain a clear solution. The extract obtained has the following characteristics:

■ Dry extract: 2.56%

■ Total sugars (glucose, fructose, manoheptulose, perseitol-HPLC): 19.5% / dry

■ Total polyphenols (Folin - Ciocalteu, gallic acid eq.): 14% / dry

■ Proteins (Bradford): 6.25% / dry.

This extract presents an antiradical activity, anti-DPPH "in tube", for which the inhibitory concentration 50 (IC50) has been determined and is 111 | jg of dry extract, which represents 10.6 | jg of polyphenols in the reaction medium.

Example 2

The dried and de-oiled avocado pulp (cake) is suspended by stirring at 10% in a 60/40 w / w glycerol / water mixture for 1 h at room temperature. The residual dry matter is separated from the liquid phase either by filtration, decantation or centrifugation, and the liquid phase thus obtained can be filtered with the aid of filters of adapted porosity in order to obtain a clear solution. The extract obtained has the following characteristics:

■ Extract 3.45%

■ Total sugars (glucose, fructose, manoheptulose, perseitol-HPLC): 19% / dry

■ Total polyphenols (Folin - Ciocalteu, gallic acid eq.): 12% / dry

■ Proteins (Bradford): 9% / dry.

This extract presents an antiradical activity, anti-DPPH "in tube", for which the inhibitory concentration 50 (IC50) has been determined and is 84 jg of dry extract, which represents 11.85 jg of polyphenols in the medium of reaction.

Example 3

The dried and deoiled avocado pulp (cake) is suspended under stirring at 10% in a 60/40 p / w propanediol / water mixture for 1 h at room temperature. The residual dry matter is separated from the liquid phase either by filtration, decantation or centrifugation, and the liquid phase thus obtained can be filtered with the aid of filters of adapted porosity in order to obtain a clear solution. The extract obtained has the following characteristics:

■ Dry extract 2.74%

■ Total sugars (glucose, fructose, manoheptulose, perseitol-HPLC): 22% / dry

■ Total polyphenols (Folin - Ciocalteu, eq. Gallic acid): 16% / dry

■ Protein (Bradford): 7% / dry.

This extract presents an antiradical activity, anti-DPPH "in tube", for which the inhibitory concentration 50 (IC50) has been determined and is 119.5 | jg of dry extract, which represents 18.5 | jg of polyphenols in the reaction medium.

Example 4: Compositions for topical application

The inventors then present several compositions for topical application. Avocado extracts rich in polyphenols (Persea gratissima et americana) can be incorporated into various cosmetic products, such as cleaning waters, oil-in-water emulsions, water-in-oil emulsions, oils, milk, lotions, shampoos, foaming products and Sprays, whose compositions are presented below.

Cleaning water for sensitive skin

Anti-aging emulsion

Milk for dry skin, atopic

Purifying cleansing cream

Anti-dandruff shampoo

Example 5: Compositions for oral administration

The avocado extracts are integrated into oral compositions, in compositions that allow the administration of 50 mg to 200 mg of avocado extract rich in polyphenols per day.

1 / Anti-stretch composition in the form of soft capsules

- Avocado extract rich in polyphenols 30 mg

- Awara 60 mg oil

- Rapeseed oil rich in unsaponifiable 300 mg

- Vitamin B group (B1, B2, B3, B5, B6, B9, B12), QSP 100% of the CDRs - Tocotrienols QSP 50% CDR

- Vitamin E

- Bee wax

- Soy lecithin

- Food gelatin

- Glycerin QSP 1 soft capsule This composition is administered from 4 to 6 capsules of 500 mg per day.

2 / Anti hair loss tablets

- Avocado extract rich in polyphenols 25 mg

- Extracts of cereals (wheat, buckwheat, millet, spelled) rich in sulfur-containing amino acids 200 mg

- Vitamin C QSP 50% of CDR - Glycosaminoglycans from fish cartilages 200 mg

- Glucidex IT 19 (compression agent) QSP

1 800 mg tablet This composition is administered from 5 to 8 tablets per day.

3 / Examples in slimming powder bar

- Avocado extract rich in polyphenols 100 mg

- Extract of tea rich in polyphenols 100 mg

- Extract of grape rich in OPC 50 mg

- Betaglucans of plant origin 100 mg

- Xanthan gum 1 mg

- 0.3 mg sodium ascorbate

- QSP maltodextrin 5 g

This composition is administered 2 times per day.

Example 6: Biological activities

1. Anti-inflammatory effect

to. Anti-inflammatory activity on keratinocytes

In the skin, the keratinocyte is one of the first cells that participates at the beginning of the inflammatory reaction in response to environmental aggression.

The "assaulted" keratinocyte will then release cytokines that will induce a cascade of reactions involving the immune system.

✓ Material and procedures:

Human keratinocytes (line NCTC-2544) have been pre-incubated or not (control) using avocado extract concentrated in polyphenols (AV) at 0.005% and 0.01% (w / v of active material) or reference molecules anti-inflammatory (dexamethasone at 10-7M, indomethacin at 10'6M) for 24 hours. The cells were then treated by the PMA at 0.1 pg / ml (Phorbol Myristate Acetate) for 24 hours, still in the presence of AV or the references.

At the end of the treatment, the amounts of secreted IL8 (interleukin 8) and PGE2 (prostaglandin E2) were measured by ELISA in the culture supernatants.

The results were analyzed statistically by means of a Student's t-test.

✓ Results and conclusion:

AV has strongly and significantly inhibited the production of inflammatory mediators IL8 and stimulated PGE2 by PMA in some keratinocytes (table 1).

The AV extract therefore has an anti-inflammatory activity

Table 1: Production of IL8 and PGE2 by keratinocytes

b. Inhibition of leukotriene B4 production for neutrophils

Leukotriene B4 (LTB4) is a lipid inflammatory mediator from the arachidonic acid pathway.

LTB4 is produced and released in significant amount by the human neutrophil polynuclear by activation of the enzyme lipoxygenase; it has an essential role in the development of cutaneous inflammatory reactions.

✓ Material and procedures:

Human neutrophils have been preincubated for 15 minutes in the presence of avocado extract concentrated in polyphenols (AV) at 0.005%; 0.01% and 0.1% (w / v of active material).

The cells are then stimulated by the addition of opsonized zymosan at 1 mg / ml.

After 10 minutes of incubation, leukotriene B4 (LTB4) released by the cells was analyzed in cell supernatants by an ELISA technique.

The results were analyzed statistically by means of a Student's t-test.

✓ Results and conclusion:

AV has significantly inhibited the production of LTB4 induced by opsonized zymosan on neutrophils (table 2).

Thus, the AV extract modulates the inflammation induced by neutrophil and LTB4.

Table 2: Production of leukotriene B4 by neutrophils

c. Inhibition of histamine release

Mast cells play an important role in allergic and inflammatory reactions; Widely distributed in man in connective tissues, such as the skin, the serous mast cell represents the sentinel cell of the local inflammatory response. Substance P, a peptide neuromediator, acts on the cutaneous mast cell, inducing a rapid release of preformed histamine in the storage granules; This mechanism of neurogenic inflammation is involved in various cutaneous pathologies.

✓ Material and procedure:

Mastocytes were preincubated for 30 minutes in the presence of avocado extract concentrated in polyphenols (AV) at 0.01% (w / v of active material) or calcium at 10 mM (reference inhibitor of histamine release).

The mast cells were then stimulated by substance P at 10 pM for 15 minutes. At the end of the incubation, the released histamine was quantified by ELISA.

The results were analyzed statistically by means of a Student's t-test.

✓ Results and conclusion:

AV has significantly inhibited the release of histamine by mast cells stimulated by substance P (Table 3).

AV extract modulates neurogenic inflammation, especially linked to histamine.

Table 3: Histamine release by mast cells

2. Depigmenting activity

The depigmenting effect of the AV extract has been studied in two different models: by evaluation of melanin production in melanocytes; and by evaluation of the enzymatic activity of tyrosinase, a key enzyme involved in the synthesis of melanin.

to. Inhibition of melanogenesis

✓ Material and procedure:

Normal human epidermal melanocytes have been cultured in the presence of 10 "7M NDP-MS (analogous to a-MSH, induction of melanogenesis) and 0.001% and 0.005% concentrated avocado extract in polyphenols (AV). p / v of active material) or of kojic acid to 0.25mM (reference).

After 240 hours of incubation, the melanin has been extracted from the cells and quantified by spectrophotometry.

The results were analyzed statistically by means of a Student's t-test.

✓ Results and conclusion:

AV has significantly inhibited melanin production by melanocytes stimulated by NDP-MSH (Table 4).

AV therefore presents a depigmenting effect.

Table 4: Production of melanin by melanocytes

b. Inhibition of tyrosinase activity

✓ Material and procedure:

The extract of avocado concentrated in polyphenols (AV), as well as the kojic acid (reference) at different concentrations in the presence of tyrosine extracted from human melanocytes for 10 minutes in cold have been preincubated.

The substrate of the enzyme, L-DOPA at 2mM, was then added.

After 1 hour of incubation at 37 ° C, the enzymatic activity has been evaluated by spectrophotometric measurement.

The results were analyzed statistically by means of a Student's t-test.

✓ Results and conclusion:

AV has significantly inhibited the enzymatic activity of tyrosinase (Table 5). This result confirms the depigmenting effect of this extract.

Table 5: Human tyrosinase activity

3. Healing activity: stimulation of re-epithelialization markers

The mechanism of healing in response to a wound involves a re-epithelialization process for the epidermal preparation.

The cutaneous re-epithelialization consists of the regeneration by keratinocytes of an organized, paved, stratified, keratinized epithelium that covers the wound and that reforms a protective barrier.

The re-epithelialization mechanism is carried out according to three stages: migration of keratinocytes, proliferation and maturation of the epidermis.

The effect of AV extract has been studied on the gene expression of markers involved in the migration phase of keratinocytes during this re-epithelialization process: laminin 5 and MMP9 (metalloprotease 9 matrix).

✓ Material and procedure:

Normal human keratinocytes were incubated for 48 hours in the presence of avocado extract concentrated in polyphenols (AV) at 0.001% and 0.005% (w / v of active material) or TGFp1 at 5 ng / ml (reference). The gene expression of MMP9 and laminin 5 (subunit y2) has been studied by real-time RT-PCR. The results were statistically analyzed by an ANOVA to a factor followed by a Dunnett's test: ns p> 0.05 (not significant); * p <0.05; *** p <0.001.

✓ Results and conclusion:

AV has significantly increased the expression of keratinocyte migration markers (table 6).

This extract therefore has an activating effect of re-epithelialization, in favor of a reparative, pro-healing effect.

Table 6: Gene Expression of Keratinocyte Migration Markers (Relative Quantity )

Laminin 5 MMP9 Control cells 1,00 1,00 Reference (TGF31) 11,33 1033% *** 19,84 1884% ***

AV 0.001% 1.62 62% * 3.81 281% ***

AV 0.005% 1.51 51% * 9.17 817% ***

Claims (11)

1. Extract of avocado fruit rich in polyphenols, containing at least 10% by weight of polyphenols and advantageously between 10 and 30% by weight of polyphenols, expressed in gallic acid equivalent to the dry extract obtained, said polyphenols containing a mixture of procyanidins, caffeic acid and caffeic acid derivatives, in a proportion of at least 70% by weight, expressed in gallic acid equivalent to the total weight content of polyphenols, and further comprising at least 10%, advantageously from 10 to 60% avocado sugars, said sugars containing at least D-manheptulose and / or perseitol, the percentages being expressed by weight with respect to the weight of the dry extract, characterized in that it is susceptible to obtained by extraction of avocado fruits that were dried in a first phase, under mild conditions, and then delipidated, and because it is capable of being obtained by solid extraction. liquid of a part of the fruit of the avocado in a solvent consisting of a binary mixture of water-type solvents and a solvent selected from glycerol or a glycol such as propanediol. 2. An extract according to claim 1, characterized in that the proportions in procyanidins, advantageously selected from the group consisting of the dimeric procyanidins of type B, the trimeric procyanidins of type A and B and the tetrameric procyanidins of type A and B, caffeic acid and Caffeic acid derivatives in said polyphenols are at least 80% by weight, expressed in gallic acid equivalent with respect to the total weight content of polyphenols. 3. Extract according to claim 1 or 2, characterized in that in the polyphenols contained in this extract, there is at least 30% of procyanidins, expressed in gallic acid equivalent with respect to the total weight content of polyphenols. 4. An extract according to any of the preceding claims, characterized in that in the polyphenols contained in this extract, caffeic acid and its derivatives are present in a proportion of at least 30% by weight, expressed in gallic acid equivalent with respect to to the total weight content of polyphenols. 5. Composition comprising, as active, an extract as defined in any one of claims 1 to 4 and an appropriate excipient, characterized in that it is a cosmetic, pharmaceutical, dermatological or nutraceutical composition. 6. The composition according to claim 5, further comprising another active ingredient, in particular selected from the group consisting of the emollients, the moisturizing active agents, the keratimulators, the keratolytics, the healing and / or restructuring agents of the skin barrier, the agents seborregulators, anti-irritant and / or anti-inflammatory agents and / or painkillers, antioxidants, anti-aging agents, depigmenting or hypopigmentation agents, pigmenting agents, lipolytic agents or inhibitors of lipogenesis or also anti-cellulite or slimming agents, filters and mineral or organic solar screens (pigmentary or ultrafine), antifungal compounds, preservatives, antibacterial agents, prebiotics and probiotics, antibiotics and immunomodulators. Composition according to claim 5 or 6, characterized in that the other active is selected from: • the healing and / or restructuring agents of the skin barrier, preferably panthenol, arabinogalactan, zinc oxide, ceramides, cholesterol, squalene and phospholipids, • seborregulatory agents, preferably selected from 5-alpha reductase inhibitors, zinc derivatives, • anti-inflammatory and / or anti-irritant and / or calming agents, preferably arabinogalactan, • hypopigmented or depigmenting agents, preferably N-undecylenyl-L-phenylalanine, • mineral or organic filters and sun screens, preferably UVB and / or UVA filters and sun screens, and • Preservatives selected preferably from capryloyl glycine, glyceryl caprylate and hexanediol. 8. Composition according to any of claims 5 to 7, further comprising at least one other active agent selected from the group consisting of: • Vegetable oils, preferably soybean oil, rapeseed oil, avocado oil, lupine oil, and advantageously sweet white lupine oil, or a mixture of these oils, • oil-diatomaceous or concentrated concentrates. vegetable or animal oil, preferably sunflower, avocado, rapeseed, maize and palm and advantageously concentrated in unsaponifiables, • unsaponifiables of vegetable or vegetable oil, preferably unsaponifiables of avocados, unsaponifiables of soybeans or their mixtures, advantageously avocado furans, and in particular, a mixture of unsaponifiables of furan avocado and unsaponifiables of soya in a respective ratio of approximately 1 / 3-2 / 3, the unsaponifiables sterol, the phytosterols, the sterol esters and the vitamin derivatives, • peptides or complexes of plant amino acids, preferably avocado peptides, lupine peptides, quinoa peptides, Maca peptides, fermented soybean peptides or not, rice peptides, • vegetable sugars, preferably avocado sugars, • Butyl avocadoate, • extracts rich in polyphenols, preferably extracts of aerial parts of Gynandropsis gynandra and extracts of Maca leaves, • the lupeol, • a total extract of lupine, • an extract of Acacia macrostachya seeds , an extract of maca leaves , an extract of Schizandra sphnanthera and a seed extract of Vigna unguiculata, • oxazolines, preferably 2-undecyl-4-hydroxymethyl-4-methyl-1,3-oxazoline, 2-undecyl-4,4-dimethyl-1,3-oxazoline, (E) -4,4-dimethyl- 2-heptadec-8-enyl-1,3-oxazoline, 4-hydroxymethyl-4-methyl-2-heptadecyl-1,3-oxazoline, (E) -4-hydroxymethyl-4-methyl-2-heptadec- 8-enyl-1,3-oxazoline, 2-undecyl-4-ethyl-4-hydroxymethyl-1,3-oxazoline and 2-undecyl-4,4-dimethyl-1,3-oxazoline, and its mixtures 9. Composition according to any of claims 5 to 8, characterized in that it is formulated to be administered topically or orally. 10. Composition according to any of claims 5 to 9, or extract as defined in any of claims 1 to 4 for use in the prevention and / or treatment of disorders or pathologies of the skin and / or mucous membranes and / or of the faneras, advantageously of the reactions or allergic, inflammatory or irritative pathologies or of the disorders of the barrier or of the homeostasis of the skin, or of the vascular disorders or also as a depigmenting and healing agent. 11. Procedure of cosmetic care of the skin and / or of the facets and / or mucous membranes, advantageously of the sensitive skin, to improve its condition and / or its appearance, in particular to favor its hydration, or also to improve the firmness , the elasticity or tonicity of the skin and fight against the accumulation of adipose tissue and skin with cellulite, or also reduce pigmentation spots, or also to prevent and / or treat aging, which comprises the administration of a cosmetic composition according to any of claims 5 to 9 or of an extract as defined according to any of claims 1 to 4.